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Dairy manure adds a substantial amount of nitrogen to wastewater due to its high levels of associated nutrients. Removal and recovery of ammonia nitrogen (NH3-N) from raw liquid dairy manure (RLDM) is greatly valued. This study was focused on the vacuum thermal stripping–acid absorption (VTS-AA) process for NH3-N from RLDM, followed by modeling and optimization. Using the response surface methodology (RSM)-based central composite design (CCD) approach, the critical operational parameters of the vacuum thermal stripping process, including temperature (50–70 °C), pH (9–11), vacuum pressure (35–55 kPa), and treatment time (60–90 min), were optimized. With the specified parameters set at temperature 69.9 °C, pH 10.5, vacuum pressure 53.5 kPa, and treatment time 64.2 min, the NH3-N removal efficiency attained was 98.58 ± 1.05%, aligning closely with the model prediction. Furthermore, the recovered ammonium sulfate ((NH4)2SO4) closely matched their commercial counterparts, confirming the effectiveness of the VTS-AA process in recovering NH3-N from RLDM. The distinct advantage of the employed technology lies in the concurrent energy demand reduction achieved by introducing a vacuum system. These findings contribute valuable insights into the practical implementation of the VTS-AA process for treating raw dairy manure, particularly in large-scale operational contexts.

Background/Objective: The tocotrienol-rich fraction (TRF) is a lipid-soluble vitamin that has good antioxidant and anti-inflammatory properties. The TRF is widely studied as a potential treatment for various diseases, including bone diseases. However, its application is limited due to its poor oral bioavailability profile, warranting an innovative approach to overcome its pharmacokinetic limitations. Recently, the nano-hydroxyapatite (nHA) has been investigated as a drug delivery vehicle for various drugs and active compounds owing to its excellent biocompatibility, biodegradability, and osteogenic properties. The nHA is also a well-known biomaterial which has chemical and structural similarities to bone minerals. Hence, we aim to explore the use of the nHA as a potential nanocarrier for the TRF. Methods: In this study, we develop and optimize the formulation of an nHA-encapsulating TRF (nHA/TRF) by employing the response surface methodology (RSM). Results: RSM outcomes reveal that the mass of the nHA, the concentration of the TRF, and the incubation time have a significant effect on the particle size, zeta potential, and encapsulation efficiency of the nHA/TRF. The outcomes for the optimized formulation are not significantly different from the predicted RSM outcomes. The optimized nHA/TRF formulation is freeze-dried and results in an average particle size of ~270 nm, a negative zeta potential value of ~−20 mV, a polydispersity index of Conclusions: Taken together, the above findings indicate that the nHA may be established as a nanocarrier for efficient delivery of the TRF, as demonstrated by the promising physical properties.

Optimizing biosurfactant (BS) production is key for sustainable industrial applications. This study investigated BS synthesis by Candida mogii using licuri oil, a renewable carbon source rich in medium-chain fatty acids. Process optimization was conducted via central composite design (CCD), adjusting concentrations of licuri oil, glucose, NH4NO3, and yeast extract. The predictive model achieved an R2 of 0.9451 and adjusted R2 of 0.8812. Under optimized conditions, C. mogii lowered water surface tension from 71.04 mN·m−1 to 28.66 mN·m−1, with a critical micelle concentration (CMC) of 0.8 g·L−1. The biosurfactant displayed high emulsification indices, exceeding 70% for canola, licuri, and motor oils, suggesting strong potential as an industrial emulsifier. FTIR and NMR analyses confirmed its glycolipid structure. Bioassays showed no toxicity to Lactuca sativa seeds, ensuring environmental safety, while antimicrobial tests demonstrated efficacy against Staphylococcus aureus and Escherichia coli, indicating its suitability as a biocidal agent. This work positions C. mogii BS from licuri oil as a promising alternative for bioremediation, biotechnology, and antimicrobial uses.

Objectives: This study aimed to develop an optimized and wide concentration range HPLC-UV method for fluconazole (FLU) determination and its adaptation for pharmacokinetics (PK) studies in the pediatric population. Methods: The following parameters of chromatographic separation were optimized: retention time, tailing factor, peak height, and the sample preconditioning parameter, such as recovery. The optimization process involved the use of a central composite design (CCD) and Box–Behnken design (BBD) in the design of experiments (DoE) approach and a multilayer perceptron (MLP) for artificial neural network (ANN) application. Statistical and PK analyses were performed using Statistica and PKanalix. Results: The acetonitrile (ACN) concentration revealed the most significant factor influencing the retention time, tailing factor, and peak height of FLU and the internal standard. For recovery, the extracting agent’s volume was the most significant factor. In most cases, the analysis conducted with the DoE and ANN indicated the same factors in a similar order regarding their impact on the analyzed variables. The optimization process allowed for achieving a wide range of determined concentrations (0.5–100 mg/L) and ~100% recovery. The developed method enabled PK analysis of 12 samples from three pediatric patients, proving its clinical usability. The estimated median clearance (CL) and volume of distribution (Vd) were 1.01 L/h and 18.64 L, respectively. Conclusions: DoE and ANNs are promising and useful tools in the optimization of sample preconditioning as well as the HPLC separation procedure. The investigated fluconazole determination method meets the European Medicines Agency (EMA) validation objectives and might be used in pediatric and adult PK studies.

This study aimed to assess the predictive performance of first- and second-order regression models in optimizing bedaquiline (BQ) solid lipid nanoparticle (SLN) formulations. A three-step central composite design and graphical optimization process was employed. A design of experiments method was used to evaluate the impact of BQ, Tween 80 (T80), polyethylene glycol (PEG), and lecithin on the formulations’ response variables, including Z-average (PSD), polydispersibility index (PdI), and Zeta potential (ZP). Secondly, we quantified the relationship between experimental variables using the regression model coefficients. Lastly, we predicted the responses and verified the models’ adequacies to ensure accurate representation and effective optimization. The first-order polynomial showed poor model adequacy and required further refinement due to its lack of explanatory power and significant predictors. Conversely, the second-order models provided superior fitness, sensitivity to variability, complexity, and prediction consistency. The optimized formulation achieved a desirability value of 0.9998, indicating alignment with the desired criteria. Specifically, the levels of BQ (19.4 mg), T80 (25.2 mg), PEG (39.2 mg), and lecithin (200 mg) corresponded to PdI (0.41), PSD (250.99 nm), and ZP (−25.95 mV). Maintaining a BQ concentration between 10 and 20% and T80 between 15 and 18% is vital for maximizing ZP and minimizing PdI and PSD, ensuring stable SLN formulations. This study underscores the significance of precise model selection and statistical analysis in pharmaceutical formulation optimization for enhanced drug delivery systems.

C-Phycocyanin (C-PC) is a photosynthetic pigment found in cyanobacteria, notably in Arthrospira species. The extraction of phycocyanobilin (PCB), the chromophore of C-PC, is a common approach to address the instability of C-PC under light, heat, and acidic conditions. Methanol is typically used for PCB extraction. However, its use poses challenges for industrial applications owing to the need for solvent removal, extensive purification, and safety validation. Therefore, this study proposes ethanol as an alternative to methanol, optimizing the ethanol extraction conditions through response surface methodology (RSM) using a central composite design (CCD) and techno-economic analysis. The parameters evaluated were the extraction temperature, time, and C-PC/solvent ratio. Optimal conditions—68.81 °C, 14.91 h, and a C-PC to solvent ratio of 1:95 (w/v)— yielded a predicted PCB yield of 29.18%, closely aligning with the actual value of 29.67 ± 1.33%. A techno-economic analysis for pilot-scale PCB production showed that optimized ethanol extraction could yield 147.13 kg/year with 506 batches, compared with 84.31 kg/year standard methanol extraction with 317 batches. Furthermore, it was evaluated to have a unit production cost of USD 1,413,588/kg, an internal rate of return (IRR) of 53.36%, and a payback time of 1.6 years with increased yields and reduced toxic solvent disposal costs. This study supports scalable PCB production with a natural blue pigment suitable for the food, beverage, and cosmetics industries.

To ascertain the significance of temperature and residence time of hydrothermal carbonization (HTC) in controlling hydrochar production, multiple regression was employed based on central composite design (CCD) to model the responses of mass yield (MY) and higher heating value (HHV). The hydrothermal reaction was explored at temperatures and times ranging from 150 to 250 °C and 0.5 to 3.5 h. Sorghum bagasse (SB) and microalgae (MA) were used to complex the reaction due to their differences in organic constituents. Simultaneously, the operating parameters were optimized by maximizing the response values under domain constraints in the HHV models. The results show that at least temperature and time in the linear system played a significant role in determining the solids recovery and the energy generation of hydrochars (p-values = 0.00), regardless of the biomass type. Moreover, the optimum conditions of SB and MA hydrochars can be achieved by increasing the temperature to the limit of 250 °C and prolonging the time to 3.5 and 3.25 h, respectively. Both respective conditions resulted in maximum HHVs of 27.54 and 35.83 MJ kg−1.

This study presents an investigation of the effects of structural characteristics, such as the layer height, infill density, top/bottom layer line directions and infill pattern, on the structural efficiency of Acrylonitrile Butadiene Styrene (ABS)-based specimens. The Fused Filament Fabrication (FFF) technique was utilized for the specimen fabrication, and the Ultimate Tensile Strength (UTS) and Strength-to-Mass (S/M) ratio were examined. The tests were planned according to the Central Composite Design (CCD), and an empirical model for each response was developed, with respect to the applied factors and their interactions. The analysis revealed that the characteristics with the strongest influence on the UTS and the S/M ratio were the infill and the layer height, respectively. Moreover, it was observed that the honeycomb structure contributed to the highest UTS compared to the other patterns. Finally, an optimization analysis based on the desirability function was performed, highlighting the combination of a 0.3 mm layer, 21.81% and 76.36% infill, 0° direction and the honeycomb pattern as the optimal for maximizing both UTS and S/M ratio under different desirability.

The aim of this study was to optimise ultrasound-assisted extraction (UAE) of the herb Sanguisorba officinalis L. in terms of the antioxidant activity (DPPH and FRAP method) and total polyphenol content (TPC). Optimisation was performed using the response surface methodology (RSM) with a third-degree (33) Central Composite Design (CCD) approach. The RSM was applied to obtain the optimal combination of (1) raw material content (2.25–7.5 g raw material/100 mL of solvent), (2) ethanol concentration (20–60% v/v), and (3) extraction time (1–15 min). The optimal conditions for the extraction of polyphenols and antioxidant potential were a raw material content of 7.5 g/100 mL of solvent (solid/solvent ratio 13.3 mL/g), an ethanol concentration of 47% v/v, and an extraction time of 10 min. At these optimal extraction parameters, the maximum extraction of polyphenols and antioxidant activity obtained experimentally was found to be very close to its predicted value and was 12.9 mmol Trolox/L (DPPH method), 19.4 mmol FeSO4/L (FRAP method), and 2.1 g GA/L (TPC). The mathematical model developed was found to fit with the experimental data on the antioxidant potential and polyphenol extraction. The n-octanol/water partition coefficient of the optimised extract was used to determine their lipophilicity. Our studies have shown that the optimised extract is highly hydrophilic (log P < 0). Optimal parameters can be used for the industrial extraction of the S. officinalis herb for the needs of, among others, the pharmaceutical or cosmetic industry.

Global warming, driven by greenhouse gases like CH4 and CO2, necessitates efficient catalytic conversion to syngas. Herein, Ni containing different molecular sieve nanomaterials are investigated for dry reforming of methane (DRM). The reduced catalysts are characterized by surface area porosity, X-ray diffraction, Raman infrared spectroscopy, CO2 temperature-programmed desorption techniques, and transmission electron microscopy. The active sites over each molecular sieve remain stable under oxidizing gas CO2 during DRM. The reduced 5Ni/CBV10A catalyst, characterized by the lowest silica–alumina ratio, smallest surface area and pore volume, and narrow 8-ring connecting channels, generated the maximum number of active sites on its outer surface. In contrast, the reduced-5Ni/CBV3024E catalyst, with the highest silica–alumina ratio, more than double the surface area and pore volume, 12-ring sinusoidal porous channels, and smallest Ni crystallite, produced the highest H2 output (44%) after 300 min of operation at 700 °C, with a CH4:CO2 = 1:1, P = 1 atom, gas hour space velocity (GHSV) = 42 L gcat−1 h−1. This performance was achieved despite having 25% fewer initial active sites, suggesting that a larger fraction of these sites is stabilized within the pore channels, leading to sustained catalytic activity. Using central composite design and response surface methodology, we successfully optimized the process conditions for the 5Ni/CBV3024E catalyst. The optimized conditions yielded a desirable H2 to CO ratio of 1.00, with a H2 yield of 91.92% and a CO yield of 89.16%, indicating high efficiency in gas production. The experimental results closely aligned with the predicted values, demonstrating the effectiveness of the optimization approach.

Composite materials are utilized in various industries due to their advantageous properties. Drilling is a crucial process for joining these materials to construct the structures. During the drilling of composite materials, several types of defect can occur, with delamination being the most prevalent. Delamination adversely effects the properties of the drilled hole and diminishes the quality of the final structure. Thrust force is a key parameter used to monitor the drilling process; a higher thrust force increases the likelihood of defects, particularly delamination, in the drilled area. In this article, a central composite design is applied to the drilling process of carbon fiber-reinforced polymer (CFRP) composites, focusing on parameters such as rotational speed, feed rate, and the angle between the composite layer sequences. The objective is to minimize delamination factors and thrust force. The effect of drilling parameters on the responses is analyzed independently. The results indicate that the derived models can predict the thrust force and delamination factors in the drilling of CFRP composites.

Developing a flow rate model for the screw feeder and optimizing discharge performance are crucial for achieving automated intelligent precision feeding. This study constructs a mass flow rate model for screw conveyors, considering the coupled structural parameters of the hopper and screw conveyor. The model is developed using single-factor tests and central composite design (CCD) response surface tests and is validated through actual discharge tests. Results indicate that the discharge rate in the hopper–screw conveyor system is primarily influenced by the screw conveyor itself. Among the structural parameters, the hopper inclination angle and the hopper discharge opening length significantly affect the filling coefficient. Validation tests show an average error of 6.8% between the predicted and simulated mass flow rates and 5.0% with the actual mass flow rate, demonstrating the model’s high precision and accuracy.

This research employs response surface methodology (RSM) to optimize and model ultra-high-performance concrete (UHPC) formulations, integrating desert sand and varying proportions of supplementary cementitious materials (SCMs), specifically fly ash (FA) and ground granulated blast furnace slag (GGBS). By investigating the influence of desert sand and SCM contents, the study aims to discern their impact on the workability and 7-day compressive strength of UHPC. Employing a central composite design (CCD), thirteen separate mixes were formulated. Key responses, namely workability and compressive strength, were evaluated. The developed models underscore the enhancement in UHPC performance through the partial replacement of cement with SCMs. Notably, an optimal combination of 75% desert sand and 30% SCMs resulted in a workability of 69.4 mm and a 7-day compressive strength of 46.01 MPa. The findings emphasize the potential for eco-friendly concrete in the construction industry, also prompting further exploration into long-term strength and higher SCM concentrations.

One interesting method for environmental remediation is the use of ZnO/ZrO2 composites in the photocatalytic degradation of lead (Pb) in wastewater. Several studies have investigated different types of composites for the removal of heavy metals from wastewater. However, the efficiency of these composites in removing the heavy metals remains debatable. Hence, this study investigated the potential of using a ZnO/ZrO2 composite for the removal of Pb from wastewater. Response surface methodology (RSM) was utilized in this work to maximize the Pb photocatalytic removal over ZnO/ZrO2 in simulated wastewater. Based on a central composite design (CCD), the experimental design included adjusting critical process parameters such as catalyst dosage, initial Pb concentration, and pH. The ZnO/ZrO2 composite was synthesized using a physical mixing technique, and its physicochemical properties were studied by field emission scanning electron microscopy (FESEM), energy dispersive X-ray spectroscopy (EDS), Fourier transform infra-red (FTIR), and X-ray diffraction (XRD). Under visible light irradiation, photocatalytic Pb removal tests were carried out in a batch reactor. The findings showed that a ZnO/ZrO2 dose of 100 mg/L, a pH of 10, and an initial Pb content of 15 ppm were the optimal conditions for maximal Pb removal (above 91.2%). The actual Pb removal obtained from the experimental runs was highly correlated with that predicted using the RSM quadratic model. The usefulness of ZnO/ZrO2 composites for photocatalytic Pb removal is demonstrated in this work, which also emphasizes the significance of RSM in process parameter optimization for improved pollutant degradation. The models that have been proposed offer significant perspectives for the development and scalability of effective photocatalytic systems intended to remove heavy metals from wastewater.

In recent years, the health-promoting properties of plant-derived compounds have garnered increasing scientific interest. Notably, tomatoes and pumpkins (Cucurbita moschata), renowned for their abundant phytochemicals and associated biological activities, have become focal points of research. This study investigated the extraction of phenolic compounds from tomatoes and pumpkins cultivated on Lemnos, an Aegean Island, aiming to enhance the nutritional profiles of food products. We established an extraction protocol for total phenolics and evaluated the antioxidant capacity using response surface methodology. Utilizing a central composite design, we optimized the extraction parameters, with time and ethanol concentration identified as critical factors (p < 0.05). The optimized extracts demonstrated substantial phenolic content (9.47 ± 0.08 and 4.52 ± 0.05 mg GAE/g for tomatoes and pumpkins, respectively) and antioxidant capabilities as determined by DPPH (7.65 ± 0.08 and 5.78 ± 0.05 μmol TE/g, respectively), ABTS (9.27 ± 0.02 and 3.95 ± 0.04 μmol TE/g, respectively), FRAP (5.25 ± 0.09 and 2.99 ± 0.03 μmol TE/g, respectively), and CUPRAC assays (2.3 ± 0.04 and 1.25 ± 0.03 μmol TE/g, respectively). Following extraction, the phenolic compounds were encapsulated using maltodextrin and subsequently freeze-dried, yielding high encapsulation efficiency. In alignment with a comprehensive strategy aimed at fostering functional snacks that enhance local economic and public health outcomes, vegetables sourced from local farms were employed to develop a savory cereal bar enriched with tomato extract and a sweet cookie infused with pumpkin extract.

A straightforward, fast and efficient analytical method was developed which utilizes a magnetic composite called three-dimensional graphene (3D-G@Fe3O4) as an adsorbent to recover nitrite ions (NO2−) from environmental water samples. The investigation into the synthesized adsorbent contained an examination of its morphology, chemical composition, structural attributes, and magnetic properties. This comprehensive analysis was conducted using various instrumental techniques, including Fourier transform-infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), Raman spectroscopy, X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET), Barrett-Joyner-Halenda (BJH), and vibrating sample magnetometry (VSM). The adsorbent surface was activated by adding cetyltrimethylammonium bromide (CTAB) to the sample solution. To improve the selectivity and sensitivity of the method, nitrite ions were reacted with sulfanilic acid and chromotropic acid sequentially. An orange-red azo-dye complex was formed in the presence of nitrite ions with a clear absorbance peak at 514 nm. The effect of the main experimental parameters such as the pH of the sample solution, adsorbent dosage, and CTAB dosage was explored, and the optimization process was performed using a central composite design (CCD). The linear dynamic range (20–100 ng mL−1) was determined under optimal experimental circumstances, yielding a reasonable determination coefficient (R2, 0.9993), a detection limit of 5.12 ng mL−1, an enrichment factor of 167, and precision values of 1.0% intraday and 2.9% inter-day. The methodology successfully identified minute nitrite ions in environmental water samples with relative recoveries that varied between 96.05 and 101.6 ng mL−1.

The influence of 3D printing parameters on compressive properties is an important factor in the application of additive manufacturing processes for products subjected to compressive loads in use. In this study, the compressive strength and compressive modulus of acrylonitrile/butadiene/styrene (ABS) test specimens fabricated using the fused deposition modeling (FDM) process were investigated with the aim of producing products of high-heeled shoes for women. The experimental part of the study includes a central composite experimental design to optimize the main 3D printing parameters (layer thickness, infill density, and extrusion temperature) and the infill geometry (honeycomb and linear at a 45° angle—L45) to achieve maximum printing properties of the 3D-printed products. The results show that the infill density has the greatest influence on the printing properties, followed by the layer thickness and, finally, the extrusion temperature as the least influential factor. The linear infill at a 45° angle resulted in higher compressive strength and lower compressive modulus values compared to the honeycomb infill. By optimizing the results, the maximum compressive strength (that of L45 is 41 N/mm2 and that of honeycomb 35 N/mm2) and modulus (that of L45 is 918 N/mm2 and that of honeycomb is 868 N/mm2) for both types of infill is obtained at a layer thickness of 0.1 mm and infill density of 40%, while the temperature for L45 can be in the range of 209 °C to 254 °C, but for the honeycomb infill, the processing temperature is 255 °C. Additionally, the study highlights the potential for sustainable manufacturing practices and the integration of advanced 3D printing technologies to enhance the efficiency and eco-friendliness of the production process.

The endo-1,4-β-xylanases (EC 3.2.1.8) are the largest group of hydrolytic enzymes that degrade xylan, the major component of hemicelluloses, by catalyzing the hydrolysis of glycosidic bonds β-1,4 in this polymer, releasing xylooligosaccharides of different sizes. Xylanases have considerable potential in producing bread, animal feed, food, beverages, xylitol, and bioethanol. The fungus Aspergillus tamarii Kita produced xylanases in Adams’ media supplemented with barley bagasse (brewer’s spent grains), a by-product from brewery industries. The culture extract exhibited two xylanase activities in the zymogram, identified by mass spectrometry as glycosyl hydrolase (GH) families 10 and 11 (GH 10 and GH 11). The central composite design (CCD) showed excellent predictive capacity for xylanase production (23.083 U mL−1). Additionally, other enzyme activities took place during the submerged fermentation. Moreover, enzymatic saccharification based on a mixture design (MD) of three different lignocellulosic residues was helpful in the production of fermentable sugars by the A. tamarii Kita crude extract.

Arthrospira platensis, known as spirulina, is a cyanobacterium with multiple nutritional benefits, as it contains substantial amounts of proteins, fatty acids, and pigments. However, the production of this microalga has faced significant challenges, primarily related to the cost and composition of the required culture medium for its optimal growth. This study focused on optimizing two nitrogen sources (urea and potassium nitrate) to maximize the growth of A. platensis and the production of phycocyanin, a photosynthetic pigment of significant commercial value. Optimization was performed using the response surface methodology (RSM) with a central composite design (CCD). Analysis of variance (ANOVA) was employed to validate the model, which revealed that the different concentrations of urea were statistically significant (p < 0.05) for biomass and phycocyanin production. However, potassium nitrate (KNO3) showed no significant influence (p > 0.05) on the response variables. The RSM analysis indicated that the optimal concentrations of KNO3 and urea to maximize the response variables were 3.5 g L−1 and 0.098 g L−1, respectively. This study offers valuable perspectives for the efficient production of A. platensis while reducing production costs for its cultivation on a larger scale.

Quetiapine fumarate (QTF) was approved for the treatment of schizophrenia and acute manic episodes. QTF can also be used as an adjunctive treatment for major depressive disorders. QTF oral bioavailability is limited due to its poor aqueous solubility and pre-systemic metabolism. The objective of the current investigation was the formulation development and manufacturing of solid self-nanoemulsifying drug delivery system (S-SNEDDS) formulation through a single-step continuous hot-melt extrusion (HME) process to address these drawbacks. In this study, Capmul® MCM, Gelucire® 48/16, and propylene glycol were selected as oil, surfactant, and co-surfactant, respectively, for the preparation of S-SNEDDS. Soluplus® and Klucel™ EF (1:1) were selected as the solid carrier. Response surface methodology in the form of central composite design (CCD) was utilized in the current experimental design to develop the S-SNEDDS formulations via a continuous HME technology. The developed formulations were evaluated for self-emulsifying properties, particle size distribution, thermal behavior, crystallinity, morphology, physicochemical incompatibility, accelerated stability, and in vitro drug release studies. The globule size and emulsification time of the optimized SNEDDS formulation was 92.27 ± 3.4 nm and 3.4 ± 3.38 min. The differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) studies revealed the amorphous nature of the drug within the formulation. There were no drug-excipient incompatibilities observed following the Fourier transform infrared (FTIR) spectroscopy. The optimized formulation showed an extended-release profile for 24 h. The optimized formulation was stable for three months (last time-point tested) at 40 °C/75% RH. Therefore, the developed S-SNEDDS formulation could be an effective oral delivery platform for QTF and could lead to better therapeutic outcomes.

In the existing investigation, the influence of wire-cut electrical discharge machining (WEDM) input factors such as pulse-on time, pulse-off time, wire tension, and taper angle on the material removal rate (MRR) on Inconel 825 was investigated. Experimental trials were performed according to the central composite design (CCD). An ANOVA test was conducted to evaluate the influence of the most significant WEDM process input parameter. The optimization of the response was achieved using the desirability approach to attain the maximum MRR. The optimum setting conditions were obtained as Ton of 0.8 µs, Toff of 38 µs, wire tension of 14 N, and taper angle of 2° for the MRR value of 2.98 g/min with a desirability of 1. Finally, the 3D surface plots were used to illustrate the variations of the output response with respect to input parameters.

Siderophores are organic ligands involved in dissolved iron (dFe) speciation in the oceans. Their study is crucial for a better understanding of the biogeochemical cycle of Fe in the marine environment, particularly in certain areas, such as the Southern Ocean, where Fe deficiency limits marine productivity. In this study, an analytical method is proposed for the extraction and pre-concentration of siderophores from seawater samples by solid phase extraction (SPE) and subsequent analysis by high-performance liquid chromatography—electrospray ionization—mass spectrometry (HPLC-ESI-MS/MS). Two siderophores were used as standards: Ferrioxamine E, a commercially available hydroxamate siderophore, and a staphyloferrin A-like compound with two citric acid units, synthesized in our laboratories by solid-phase peptide synthesis. A central composite design, considering different pH (2, 3.5, and 5) and sample loading volume (50, 125 and 200 mL) as variables, was used to optimize the extraction yield with SPE C18 cartridges. Tests were conducted on samples of artificial seawater spiked with siderophore standards. Ferrioxamine E showed high extraction yields in all tests carried out. On the contrary, the extraction of staphyloferrin A-like compound was significantly affected by both pH and loading volume.

Polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) are recognized as carcinogens and mutagenic food contaminants that threaten public health. As for food safety aspects, control of these contaminants in processed and fatty food is necessary. In this study, eleven factors were screened by the Plackett–Burman design, and four variables were chosen to optimize with the central composite design (CCD) for the improvement of extraction and cleanup procedures of these food contaminants. The optimized variables include 5 g of sample, 2 mL mixture of 2/2/1 ethyl acetate/acetone/isooctane, 1.6 g of ammonium formate, 0.9 g of sodium chloride, and 0.25 g of sorbent Z-Sep+. A 5 min cleanup vortex time with the spike calibration curve strategy, analyzed by gas chromatography–mass spectrometry (GC-MS), led to the validated limits of quantification (LOQs) for 16 PAHs and 36 PCBs of 0.5–2 and 0.5–1 ng/g, respectively, and recoveries of 72–120%, with an average relative standard deviation (%RSD) of 17, for PAHs, and 80–120%, with an %RSD of 3, for PCBs. The method introduces excellent accuracy, precision, and efficiency, and minimizes matrix effects, and ensures a control procedure, adopted with international standards, for food authorities to determine the contaminants of interest in processed meat, and consequently, prevent food-borne disease to improve public health indices.

In this study, a composite material consisting of three-dimensional graphene aerogel and iron oxide nanoparticles (3DG/Fe3O4) was created and utilized for the purpose of magnetic solid-phase extraction (MSPE) of thirteen polycyclic aromatic hydrocarbon (PAH) compounds via gas chromatography–mass spectrometry/selected ion monitoring (GC-MS/SIM) analysis. The synthesized adsorbent underwent a range of characterization techniques, including scanning electron microscopy, vibrating sample magnetometry, Raman spectroscopy, X-ray diffraction, Brunauer–Emmett–Teller, Fourier transform-infrared spectroscopy, and Barrett–Joyner–Halenda techniques, to examine its properties and morphology. The synthesized adsorbent integrates the benefits of superior adsorption capacity from modified graphene oxide (GO) with the magnetic separability of magnetite microparticles, resulting in a high adsorption capacity with easy separation from sample solutions. The efficiency of the proposed method was optimized and modeled using a central composite design (CCD), which considered the primary factors influencing it. The optimal conditions were obtained as the adsorbent dosage of 10 mg, the extraction time of 4 min, and the salt concentration of 3% w/v. The limit of detection for the target PAHs was established to range from 0.016 to 0.2 ng mL−1 in optimal conditions, exhibiting a signal-to-noise ratio of 3. The linear dynamic range spanned from 5 to 100 ng mL−1, with determination coefficients (R2) ranging from 0.9913 to 0.9997. The intra- and inter-day precisions were calculated as relative standard deviations (RSDs) equal to 3.9% and 4.7%, respectively. The proposed method was successfully applied to the determination of PAHs in water samples (tap, river, and rainwater), and recoveries in the range of 71–110% (RSDs < 5.2%, n = 3) were obtained.

Microbial fermentation for the production of tetramethylpyrazine (TTMP) is considered to be the most promising method, and the development of a cheap fermentation substrate is of great importance for large-scale TTMP production. In this study, inexpensive by-products from the food industry, i.e., molasses and soybean meal (instead of glucose and tryptone), were used as substrates for TTMP fermentation. The pretreatment of soybean meal was explored in order to achieve a better fermentation effect. The contents of each component in the fermentation medium were optimized by central composite design (CCD). The optimum contents were as follows: 72.5 g/L of molasses, 37.4 g/L of diammonium hydrogen phosphate (DAP), 53.4 g/L of soybean meal, and 5 g/L of yeast powder. The software predicted a maximum TTMP yield of 1469.03 mg/L, and the actual TTMP yield was 1328.95 mg/L for the validation experiment in the optimum medium. Under the optimum conditions (72.5 g/L of molasses, 37.4 g/L of DAP, 53.4 g/L of soybean meal, and 5 g/L of yeast powder), the actual maximum TTMP yield (1328.95 mg/L) in this study was much higher than the TTMP yield (895.13 mg/L) under the conditions (150 g/L of molasses, 30 g/L of DAP, 30 g/L of tryptone, and 10 g/L of yeast powder) of our previous study published in Molecules. In this study, the TTMP yield improved by 48.46%, with decreased molasses (more than half), decreased yeast powder (half) and by-product soybean meal instead of tryptone compared to our previous study. In summary, the cheaper fermentation medium had a higher TTMP yield in this study, which improves the application potential of Bacillus sp. TTMP20.

The promising therapeutic implications of nanoparticles have spurred their development for biomedical applications. An eco-friendly methodology synthesizes gold nanoparticles using Cordyceps militaris, an edible mushroom (Cord-Au-NPs), using a quality-by-design approach (central composite design). UV-visible spectroscopy analysis revealed an absorption peak at 540–550 nm, thus confirming the synthesis of gold nanoparticles. Cord-Au-NPs have a crystalline structure, as evidenced by the diffraction peaks. The zeta potential value of −19.42 mV signifies the stability of Cord-Au-NPs. XRD study shows gold facets and EDX analysis revealed a strong peak of spherical nanoparticles in the gold region with a mean particle size of 7.18 nm and a polydispersity index of 0.096. The obtained peaks are closely associated with phenolic groups, lipids, and proteins, as examined by FTIR, suggesting that they function as the reducing agent. Cord-Au-NPs exhibited dose-dependent antioxidant, antidiabetic, and antibacterial activity. The method is eco-friendly, nontoxic, less time-consuming, and does not use synthetic materials, leading to higher capabilities in biomedical applications.

A virtual experiment conducted using the ICP-MS TuneSim software served as the basis for studies that compared the applicability of the central composite design with the Box–Behnken design in analytical chemistry applications. The insights gathered from these virtual experiments were used in real-life electroanalytical tests, including the determination of germanium and the studies of the antioxidant properties of herbal infusions. The experimental design and interpretation of the results were performed using Statistica software.

Hippophae rhamnoides L. leaves possess a remarkable amount of polyphenols that could serve as a natural remedy in various applications. In comparison, numerous techniques, such as conventional and high-pressure techniques, are available for extracting the bioactive fractions from sea buckthorn leaves (SBL). However, enzyme-assisted extraction (EAE) of SBL has not been comprehensively studied. The aim of this study was to optimize critical EAE parameters of SBL using the cellulolytic enzyme complex, Viscozyme L, to obtain a high-yield extract with a high concentration of bioactive compounds. In order to determine the optimal conditions for EAE, the study employed a central composite design and response surface methodology to analyze the effects of four independent factors (pH, temperature, extraction time, and enzyme concentration) on two different responses. Our findings indicated that under optimal conditions (3:15 h extraction, temperature 45 °C, pH 4.9, and 1% Viscozyme L v/w of leaves DW), EAE yielded 28.90 g/100 g DW of the water-soluble fraction. Furthermore, the EAE-optimized liquid extract was continuously fermented using an ancient fermentation starter, Tibetan kefir grains, which possess lactic acid bacteria (LAB) and have significant potential for use in biopreservation. Interestingly, the results indicated various potential prebiotic characteristics of LAB. Additionally, alterations in the cell wall morphology of the SBL residue after EAE were examined using scanning electron microscopy (SEM). This study significantly optimized EAE parameters for sea buckthorn leaves, providing a promising natural source of bioactive compounds for various applications, such as nutraceuticals, functional foods, and high-value products.

The oleaginous bacterium Rhodococcus erythropolis JCM3201T offers various unique enzyme capabilities, and it is a potential producer of industrially relevant compounds, such as triacylglycerol and carotenoids. To develop this strain into an efficient production platform, the characterization of the strain’s nutritional requirement is necessary. In this work, we investigate its substrate adaptability. Therefore, the strain was cultivated using nine nitrogen and eight carbon sources at a carbon (16 g L−1) and nitrogen (0.16 g L−1) weight ratio of 100:1. The highest biomass accumulation (3.1 ± 0.14 g L−1) was achieved using glucose and ammonium acetate. The highest lipid yield (156.7 ± 23.0 mg g−1DCW) was achieved using glucose and yeast extract after 192 h. In order to enhance the dependent variables: biomass, lipid and carotenoid accumulation after 192 h, for the first time, a central composite design was employed to determine optimal nitrogen and carbon concentrations. Nine different concentrations were tested. The center point was tested in five biological replicates, while all other concentrations were tested in duplicates. While the highest biomass (8.00 ± 0.27 g L−1) was reached at C:N of 18.87 (11 g L−1 carbon, 0.583 g L−1 nitrogen), the highest lipid yield (100.5 ± 4.3 mg g−1DCW) was determined using a medium with 11 g L−1 of carbon and only 0.017 g L−1 of nitrogen. The highest carotenoid yield (0.021 ± 0.001 Abs454nm mg−1DCW) was achieved at a C:N of 12 (6 g L−1 carbon, 0.5 g L−1 nitrogen). The presented results provide new insights into the physiology of R. erythropolis under variable nutritional states, enabling the selection of an optimized media composition for the production of valuable oleochemicals or pigments, such as rare odd-chain fatty acids and monocyclic carotenoids.

Tomato plant waste (TPW) is a significant agricultural byproduct that has been often underutilized. Recent studies have shown that its use to obtain methane in an anaerobic digestion (AD) process is viable. However, there is not much information available on studies to improve methane production from this substrate using statistical methods for optimization processes such as central composite design (CCD). For this investigation, CCD was adopted to analyze the effect of S/I ratio (substrate/inoculum ratio) (0.32–1.12), temperature (27–43 °C), and inoculum concentration (10.35–20.95 g VS/L) on methane generation and volatile solids (VS) removal in a batch AD system mono-digestion of TPW. The highest average value of methane yield was found to be 210.8 mL CH4/g VS (S/I ratio 0.48, 40 °C, and 18.80 g VS/L), and the highest average value of VS removal was found to be 36.9% (S/I ratio 1.12, 35 °C, and 15.65 g VS/L). We obtain a model with a better fit for the VS removal (R2 = 0.9587) than for the methane production (R2 = 0.9156). Temperature and S/I ratio were the factors most important for methane production and VS removal, respectively.

As a chemical platform, 2,3-Butanediol (2,3-BD) has been widely applied in various industrial fields. In this study, to enhance the production of 2,3-BD by Saccharomyces cerevisiae L7, Plackett–Burman (PB) multifactorial design, the steepest climb test and central composite design (CCD) were employed to optimize the culturing conditions of S. cerevisiae L7. The results show that acetic acid, peptone and glucose were contributing factors for 2,3-BD production. Subsequently, a satisfactory production of 2,3-BD (13.52 ± 0.12 g/L) was reached under optimal conditions, which was 3.12 times higher than before optimization. Furthermore, fed-batch fermentation was carried out under optimized culture conditions, and a higher production and yield efficiency of 2,3-BD were achieved (21.83 ± 0.56 g/L and 0.15 ± 0.01 g/g, respectively) when glucose (20 g/L) and acetic acid (0.2 g/L) were added at 12, 24, 36, 48 and 60 h. Therefore, the production and yield efficiency of 2,3-BD were higher than those without fed-batch fermentation (61.46% and 58.51%, respectively). These results provide good support and a technical foundation for the large-scale industrial production of 2,3-BD by Saccharomyces cerevisiae.

Glaucoma is a progressive optic neuropathy characterized by a rise in the intraocular pressure (IOP) leading to optic nerve damage. Bimatoprost is a prostaglandin analogue used to reduce the elevated IOP in patients with glaucoma. The currently available dosage forms for Bimatoprost suffer from relatively low ocular bioavailability. The objective of this study was to fabricate and optimize solid lipid nanoparticles (SLNs) containing Bimatoprost for ocular administration for the management of glaucoma. Bimatoprost-loaded SLNs were fabricated by solvent evaporation/ultrasonication technique. Glyceryl Monostearate (GMS) was adopted as solid lipid and poloxamer 407 as surfactant. Optimization of SLNs was conducted by central composite design. The optimized formulation was assessed for average particle size, entrapment efficiency (%), zeta potential, surface morphology, drug release study, sterility test, isotonicity test, Hen’s egg test-chorioallantoic membrane (HET-CAM) test and histopathology studies. The optimized Bimatoprost-loaded SLNs formulation had an average size of 183.3 ± 13.3 nm, zeta potential of −9.96 ± 1.2 mV, and encapsulation efficiency percentage of 71.8 ± 1.1%. Transmission electron microscopy (TEM) study revealed the nearly smooth surface of formulated particles with a nano-scale size range. In addition, SLNs significantly sustained Bimatoprost release for up to 12 h, compared to free drug (p < 005). Most importantly, HET-CAM test nullified the irritancy of the formulation was verified its tolerability upon ocular use, as manifested by a significant reduction in mean irritation score, compared to positive control (1% sodium dodecyl sulfate; p < 0.001). Histopathology study inferred the absence of any signs of cornea tissue damage upon treatment with Bimatoprost optimized formulation. Collectively, it was concluded that SLNs might represent a viable vehicle for enhancing the corneal permeation and ocular bioavailability of Bimatoprost for the management of glaucoma.

Amitriptyline residue released into the aquatic ecosystem can have detrimental consequences on marine organisms and human wellbeing via consumption of polluted water. With a uniquely large surface area and abundant functionalities, graphene oxide adsorption offers a remediation solution for such water pollution. This study focused on synthesizing a novel graphene-based adsorbent via ice-templating of boron-doped graphene substrate. The batch adsorption performance of the as-synthesized adsorbent was explored by central composite design (CCD), while its potential large-scale application was evaluated with a packed-bed column study. The CCD optimized conditions of 12.5 mg dosage, 32 min adsorption time, 30 °C operating temperature and 70 ppm concentration produced the highest removal efficiency of 87.72%. The results of the packed-bed study indicated that continuous adsorption of amitriptyline was best performed at a graphene bed of 3.5 cm in height, with 100 ppm of the pharmaceutical solution flowing at 2 mL/min. Furthermore, the breakthrough curve was effectively portrayed by the Log Bohart–Adams model. The as-synthesized adsorbent showed a high regeneration potential using ethanol eluent via multiple adsorption–desorption cycles. The results suggest the boron-doped graphene adsorbent in packed-bed as a highly effective system to remediate amitriptyline in an aqueous environment.

Benzalkonium chloride (BAC) is one of the most commonly used quaternary ammonium compounds in the pharmaceutical, cosmetic, and food industries. The aim of our study was to compare the physiological responses of Escherichia coli MSCL 332, Pseudomonas putida MCCL 650, and Staphylococcus epidermidis MSCL 333 on 50 mg/L BAC in rich and poor medium (100% and 5% tryptone soya broth (TSB)) in the temperature range from 8 °C to 37 °C, under static and shaking conditions. A high-throughput, 96-well microplate method was used to compare a broad range of cultivation conditions. The effect of BAC on growth, biofilm formation activity, and dehydrogenase and fluorescein diacetate hydrolysis activity was evaluated. Addition of BAC to 100% TSB inhibited biofilm formation at 37 °C by 2.4, 1.8, and 1.6 times for E. coli, P. putida, and S. epidermidis, respectively. In turn, BAC stimulated biofilm formation in E. coli in 5% TSB at 37 °C and 100% TSB at 8 °C, i.e., 1.4 and 1.3 times, respectively. Statistical optimization of broth composition with emphasis on biofilm formation and further testing under experimental conditions was performed with P. putida.

Curcumin is a potent natural compound used to treat Alzheimer’s disease (AD). However, the clinical usefulness of curcumin to treat AD is restricted by its low oral bioavailability and difficulty permeating the blood-brain barrier. To overcome such drawbacks, various alternative strategies have been explored, including the transnasal route. However, rapid mucociliary clearance in the nasal cavity is a major hindrance to drug delivery. Thus, designing a delivery system for curcumin to lengthen the contact period between the drug and nasal mucosa must be employed. This study describes the optimization of KLVFF conjugated curcumin microemulsion-base hydrogel (KCMEG) to formulate a prototype transnasal preparation using the response surface method to improve a mucoadhesive property. A central composite design was employed to optimize and evaluate two influencing factors: the concentration of carbopol 940 and the percentage of KLVFF conjugated curcumin microemulsion (KCME). The physicochemical properties, anti-cholinesterase activity, and anti-aggregation activities of KCME were investigated in this study. The studied factors, in terms of main and interaction effects, significantly (p < 0.05) influenced hardness and adhesiveness. The optimized KCMEG was evaluated for pH, spreadability, and mucoadhesive properties. Ex vivo nasal ciliotoxicity to optimize KCMEG was performed through the porcine nasal mucosa. KCME was transparent, with a mean globule size of 70.8 ± 3.4 nm and a pH of 5.80 ± 0.02. The optimized KCMEG containing 2% carbopol 940 showed higher in vitro mucoadhesive potential (9.67 ± 0.13 min) compared with microemulsion and was also found to be free from nasal ciliotoxicity during histopathologic evaluation of the porcine nasal mucosa. The result revealed that both the concentration of carbopol 940 and the percentage of KCME play a crucial role in mucoadhesive properties. In conclusion, incorporating a mucoadhesive agent in a microemulsion can increase the retention time of the formulation, leading to enhanced brain delivery of the drug. Findings from the investigation revealed that KCMEG has the potential to constitute a promising approach to treating AD via transnasal administration.

This study aimed to analyze the factors that impact the cloud point extraction of ciprofloxacin, levofloxacin, and moxifloxacin. The following independent variables were analyzed: Triton X-114 concentration, NaCl concentration, pH, and incubation temperature. The dependent variable studied was recovery. A central composite design model was used. The applied quantitation method was HPLC. The method was validated for linearity, precision, and accuracy. The results underwent ANOVA® analysis. The polynomial equations were generated for each analyte. The response surface methodology graphs visualized them. The analysis showed that the factor most affecting the recovery of levofloxacin is the concentration of Triton X-114, while the recovery of ciprofloxacin and moxifloxacin is most affected by pH value. However, the concentration of Triton X-114 also plays an important role. The optimization resulted in the following recoveries: for ciprofloxacin, 60%; for levofloxacin, 75%; and for moxifloxacin, 84%, which are identical to those estimated with regression equations—59%, 74% and 81% for ciprofloxacin, levofloxacin, and moxifloxacin, respectively. The research confirms the validity of using the model to analyze factors affecting the recovery of the analyzed compounds. The model allows for a thorough analysis of variables and their optimization.

Response surface methodology (RSM) is used in this study to optimize the thermal characteristics of single graphene nanoplatelets and hybrid nanofluids utilizing the miscellaneous design model. The nanofluids comprise graphene nanoplatelets and graphene nanoplatelets/cellulose nanocrystal nanoparticles in the base fluid of ethylene glycol and water (60:40). Using response surface methodology (RSM) based on central composite design (CCD) and mini tab 20 standard statistical software, the impact of temperature, volume concentration, and type of nanofluid is used to construct an empirical mathematical formula. Analysis of variance (ANOVA) is applied to determine that the developed empirical mathematical analysis is relevant. For the purpose of developing the equations, 32 experiments are conducted for second-order polynomial to the specified outputs such as thermal conductivity and viscosity. Predicted estimates and the experimental data are found to be in reasonable arrangement. In additional words, the models could expect more than 85% of thermal conductivity and viscosity fluctuations of the nanofluid, indicating that the model is accurate. Optimal thermal conductivity and viscosity values are 0.4962 W/m-K and 2.6191 cP, respectively, from the results of the optimization plot. The critical parameters are 50 °C, 0.0254%, and the category factorial is GNP/CNC, and the relevant parameters are volume concentration, temperature, and kind of nanofluid. From the results plot, the composite is 0.8371. The validation results of the model during testing indicate the capability of predicting the optimal experimental conditions.

The primary goals of this study were to identify the influence of temperature and drying time on pretreated cassava flour, as well as the optimal settings for the factors and to analyze the microstructure of cassava flour. The experiment was designed using the response surface methodology with central composite design and the superimposition approach in order to assess the effect of drying temperature (45.85–74.14 °C) and drying time (3.96–11.03 h) and the optimal drying conditions of the cassava flour investigated. Soaking and blanching were applied as pretreatments to freshly sliced cassava tubers. The value moisture content of cassava flour was between 6.22% and 11.07%, whereas the observed whiteness index in cassava flour ranged from 72.62 to 92.67 in all pretreated cassava flour samples. Through analysis of variance, each drying factor, their interaction, and all squared terms had a substantial impact on moisture content and whiteness index. The optimized values for drying temperature and drying time for each pretreated cassava flour were 70 °C and 10 h, respectively. The microstructure showed a non-gelatinized, relatively homogeneous in size and shape sample with pretreatment soaked in distilled water at room temperature. These study results are relevant to the development of more sustainable cassava flour production.

Eliminating hazardous contaminants is a necessity for maintaining a healthy environment on Earth. This work used a sustainable method to create Iron–Zinc nanocomposites with polyvinyl alcohol assistance. Mentha Piperita (mint leaf) extract was used as a reductant in the green synthesis of bimetallic nanocomposites. Doping with Poly Vinyl Alcohol (PVA) caused a reduction in crystallite size and greater lattice parameters. XRD, FTIR, EDS, and SEM techniques were used to establish their surface morphology and structural characterization. The high-performance nanocomposites were used to remove malachite green (MG) dye using the ultrasonic adsorption technique. Adsorption experiments were designed by central composite design and optimized by response surface methodology. According to this study, 77.87% of the dye was removed at the optimum optimized parameters (10.0 mg L−1 was the concentration of MG dye at a time of 8.0 min, pH 9.0, and 0.02 g of adsorbent amount) with adsorption capacity up to 92.59 mg·g−1. The dye adsorption followed Freundlich’s isotherm model and the pseudo-second-order kinetic model. Thermodynamic analysis affirmed the spontaneous nature of adsorption due to negative ΔGo values. As a result, the suggested approach offers a framework for creating an effective and affordable technique to remove the dye from a simulated wastewater system for environmental conservation.

Naphthalene is a carcinogenic compound and its environmental release poses a major risk to human and aquatic health. Therefore, the application of nanomaterial technologies for naphthalene removal from wastewater has attracted significant attention. In this research, for the first time, the performance of IRMOF-3 for naphthalene removal from aqueous media is evaluated. IRMOF-3 with a specific surface area of 718.11 m2·g−1 has the ability to absorb naphthalene from synthetic wastewater to a high extent. The structures and morphology of IRMOF-3 were determined by FT-IR, XRD, SEM and BET analyses. Thirty adsorption experiments were conducted to obtain the best conditions for naphthalene removal. An optimum naphthalene removal efficiency of 80.96% was obtained at IRMOF-3 amounts of 0.1 g·L−1, a solution concentration of 15 mg·L−1, a contact time of 60 min and a pH = 11. The results indicate that the lower the concentration of naphthalene, the higher its dispersion at the surface of the porous nanostructure. Increasing naphthalene concentration results in its accumulation on porous nanostructures that clog cavities. In addition, high contact time provides ample opportunity for naphthalene to penetrate the cavities and pores which facilitates crystallization phenomena deep in the pores. Finally, the results of this study revealed that IRMOF-3 is one of the most effective adsorbents for naphthalene removal from wastewater.

This research focuses on optimizing fermentation modification and papain enzymes. In manufacturing virgin coconut oil using the response surface methodology (RSM), the experiment was carried out based on the Central Composite Design (CCD). Coconut oil yield, as a function of crude papain enzyme (CPE) mass (0–1 g) and fermentation time (12–60 h), was observed for 13 runs. The yield of virgin coconut oil with natural fermentation without the addition of crude enzyme papain is 19%, and with the addition of 1 g of the enzyme, it can reach a maximum of 27.7%. Optimal conditions were obtained at a mass of crude papain enzyme 993.5 mg, fermentation time 60 h respectively, yields: Banda Aceh virgin coconut oil (BAVCO) 28.4%, Pidie Jaya virgin coconut oil (PJVCO) 25.6%, and Bireuen virgin coconut oil (BVCO) 24.7%, quality of virgin coconut oil (VCO): water content (WC) 0.047%, free fatty acid (FFA) 0.01%, and peroxide (PN) 0.024% from each of the total mass of 300 g grated coconut, VCO modified by fermentation with the addition of CPE increased the yield. The quality of VCO in terms of WC, FFA, and PN meets the VCO quality standard. The optimization for desirability was 0.998, and the product had a transparent color, a distinct aroma, and did not have a putrid aroma.

A polyethylene terephthalate (PET)-degrading bacterium identified as Stenotrophomonas maltophilia PRS8 was isolated from the soil of a landfill. The degradation of the PET bottle flakes and the PET prepared as a powder were assessed using live cells, an extracellular medium, or a purified cutinase-like enzyme. These treated polymers were analyzed using Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The depolymerization products, identified using HPLC and LC-MS, were terephthalic acid (TPA), mono(2-hydroxyethyl)-TPA (MHET), and bis(2-hydroxyethyl)-TPA (BHET). Several physicochemical factors were optimized for a better cutinase-like enzyme production by using unique single-factor and multi-factor statistical models (the Plackett–Burman design and the central composite design software). The enzyme was purified for homogeneity through column chromatography using Sephadex G-100 resin. The molecular weight of the enzyme was approximately 58 kDa. The specific activity on para nitrophenyl butyrate was estimated at 450.58 U/mg, with a purification of 6.39 times and a yield of 48.64%. The enzyme was stable at various temperatures (30–40 °C) and pH levels (8.0–10.0). The enzyme activity was significantly improved by the surfactants (Triton X-100 and Tween-40), organic solvent (formaldehyde), and metals (NiCl2 and Na2SO4). The extracellular medium containing the cutinase-type enzyme showed a depolymerization yield of the PET powder comparable to that of Idonella skaiensis IsPETase and significantly higher than that of Humicola insolens thermostable HiCut (HiC) cutinase. This study suggests that S. maltophilia PRS8 is able to degrade PET at a mesophilic temperature and could be further explored for the sustainable management of plastic waste.

The present study utilized response surface methodology (RSM) and Bayesian neural network (BNN) to predict the characteristics of a diesel engine powered by a blend of biodiesel and diesel fuel. The biodiesel was produced from waste cooking oil using a biocatalyst synthesized from vegetable waste through the wet impregnation technique. A multilevel central composite design was utilized to predict engine characteristics, including brake thermal efficiency (BTE), nitric oxide (NO), unburned hydrocarbons (UBHC), smoke emissions, heat release rate (HRR), and cylinder peak pressure (CGPP). BNN and the logistic–sigmoid activation function were used to train the experimental data in the artificial neural network (ANN) model, and the errors and correlations of the predicted models were calculated. The study revealed that the biocatalyst was capable of producing a maximum yield of 93% at 55 °C under specific reaction conditions, namely a reaction time of 120 min, a stirrer speed of 900 rpm, a catalyst loading of 7 wt.%, and a molar ratio of 1:9. Further, the ANN model was found to exhibit comparably lower prediction errors (0.001–0.0024), lower MAPE errors (3.14–4.6%), and a strong correlation (0.984–0.998) compared to the RSM model. B100-80%-20% was discovered to be the best formulation for emission property, while B100-90%-10% was the best mix for engine performance and combustion at 100% load. In conclusion, this study found that utilizing the synthesized biocatalyst led to attaining a maximum biodiesel yield. Furthermore, the study recommends using ANN and RSM techniques for accurately predicting the characteristics of a diesel engine.

The optimization of extraction by using solvents of phenolic compounds (TPh) of grape pomace (GP) based on a central composite design was investigated. The GP was characterized, and preliminary assays were conducted with five different solvents (water, ethanol, acetone, methanol, and butanol) and the aqueous mixtures thereof. Ethanol and acetone were revealed to be the best solvents for TPh extraction. The main extraction parameters (temperature—T, time—t, solvent concentration, and liquid–solid ratio—L/S) were optimized by using a central composite design. The optimized conditions for the ethanol extraction (T = 60 °C, t = 1.5 h, L/S = 25 mL/gdryGP) and for acetone (T = 50 °C, t = 1.5 h, L/S = 25 mL/gdryGP) were determined. Single-stage extraction revealed a TPh of 45.18 ± 9.51 mgGAE/gdryGP for acetone and a TPh of 38.70 ± 3.64 mgGAE/gdryGP for ethanol. The characterization of the extracts revealed the presence of gallic acid, caffeic acid, syringic acid, vanillic acid, chlorogenic acid, and p-coumaric acid, where the concentration of the first three compounds stands out in all extracts. A three-stage extraction increased the yield of ethanol to 63.3 mg GAE/gdryGP and the yield of acetone to 59.2 mg GAE/gdryGP. Overall, both solvents allow the extraction of phenolic compounds of grape pomace, but ethanol is commonly considered a greener solvent for this purpose.

Olmesartan medoxomil (OLM) is a first-line antihypertensive drug with low oral bioavailability (28.6%). This study aimed to develop oleogel formulations to decrease OLM side effects and boost its therapeutic efficacy and bioavailability. OLM oleogel formulations were composed of Tween 20, Aerosil 200, and lavender oil. A central composite response surface design chose the optimized formulation, containing Oil/Surfactant (SAA) ratio of 1:1 and Aerosil % of 10.55%, after showing the lowest firmness and compressibility, and the highest viscosity, adhesiveness, and bioadhesive properties (Fmax and Wad). The optimized oleogel increased OLM release by 4.21 and 4.97 folds than the drug suspension and gel, respectively. The optimized oleogel formulation increased OLM permeation by 5.62 and 7.23 folds than the drug suspension and gel, respectively. The pharmacodynamic study revealed the superiority of the optimized formulation in maintaining normal blood pressure and heart rate for 24 h. The biochemical analysis revealed that the optimized oleogel achieved the best serum electrolyte balance profile, preventing OLM-induced tachycardia. The pharmacokinetic study showed that the optimized oleogel increased OLM’s bioavailability by more than 4.5- and 2.5-folds compared to the standard gel and the oral market tablet, respectively. These results confirmed the success of oleogel formulations in the transdermal delivery of OLM.

Bone-specific functionalization strategies on liposomes are promising approaches to delivering the drug in osteoporotic conditions. This approach delivers the drug to the bone surface specifically, reduces the dose and off-target effects of the drug, and thereby reduces the toxicity of the drug. The purpose of the current research work was to fabricate the bone-specific peptide conjugated pegylated nanoliposomes to deliver anabolic drug and its physicochemical evaluations. For this, a bone-specific peptide (SDSSD) was synthesized, and the synthesized peptide was conjugated with a linker (DSPE-PEG2000-COOH) to obtain a bone-specific conjugate (SDSSD-DSPE). Purified SDSSD-DSPE was characterized by HPLC, Maldi-TOF, NMR, and Scanning Electron Microscope/Energy Dispersive Spectroscopy (SEM/EDS). Further, peptide-conjugated and anabolic drug-encapsulated liposomes (SDSSD-LPs) were developed using the ethanol injection method and optimized by Central Composite Design (CCD) using a statistical approach. Optimized SDSSD-LPs were evaluated for their physicochemical properties, including surface morphology, particle size, zeta potential, in vitro drug release, and bone mineral binding potential. The obtained results from these studies demonstrated that SDSSD-DSPE conjugate and SDSSD-LPs were optimized successfully. The particle size, % EE, and zeta potential of SDSSD-LPs were observed to be 183.07 ± 0.85 nm, 66.72 ± 4.22%, and −25.03 ± 0.21 mV, respectively. SDSSD-LPs demonstrated a sustained drug release profile. Further, the in vitro bone mineral binding assay demonstrated that SDSSD-LPs deliver the drug to the bone surface specifically. These results suggested that SDSSD-LPs could be a potential targeting approach to deliver the anabolic drug in osteoporotic conditions.

A mucoadhesive microemulsion of lipophilic silymarin (SLMMME) was developed to treat Parkinson’s disease (PD). Optimization of the SLM microemulsion (ME) was performed using Central Composite Design (CCD). The composition of oil, surfactant, co-surfactant, and water was varied, as per the design, to optimize their ratio and achieve desirable droplet size, zeta potential, and drug loading. The droplet size, zeta potential, and drug loading of optimized SLMME were 61.26 ± 3.65 nm, −24.26 ± 0.2 mV, and 97.28 ± 4.87%, respectively. With the addition of chitosan, the droplet size and zeta potential of the developed ME were both improved considerably. In vitro cell toxicity investigations on a neuroblastoma cell line confirmed that SLMMME was non-toxic and harmless. In comparison to ME and drug solution, mucoadhesive ME had the most flow through sheep nasal mucosa. Further, the in vitro release showed significantly higher drug release, and diffusion of the SLM loaded in MEs than that of the silymarin solution (SLMS). The assessment of behavioral and biochemical parameters, as well as inflammatory markers, showed significant (p < 0.05) amelioration in their level, confirming the significant improvement in neuroprotection in rats treated with SLMMME compared to rats treated with naïve SLM.

Background: Antihypertensive drug telmisartan (TEL) belongs to BCS class II, which is characterized by low water solubility and, consequently, low oral bioavailability. Gastroretentive systems may overcome the problems associated with low solubility of TEL and incomplete absorption by localizing the drug release in the stomach. The purpose of this study was to prepare TEL-loaded, oil-entrapped, floating alginate beads with the intent of enhancing the oral bioavailability of TEL for the treatment of hypertension. Methods: For the formulation and optimization of seventeen formulations of TEL-loaded oil-entrapped floating alginate beads, a central composite design was utilized. The concentration of sodium alginate (X1), the concentration of cross-linker (X2), and the concentration of sesame oil (X3) served as independent variables, whereas the entrapment efficiency (Y1), in vitro buoyancy (Y2), and drug release Q6h (Y3) served as dependent variables. Using the emulsion gelation method and calcium chloride as the cross-linking agent, different formulations of TEL alginate beads were produced. All formulations were evaluated for their entrapment efficiency percentage, in vitro buoyancy, and in vitro drug release. The optimal formulation of TEL alginate beads was prepared with and without oil and evaluated for entrapment efficiency percentage, in vitro buoyancy, swelling ratio, average size, and in vitro drug release. Using scanning electron microscopes, the surface morphology was determined. Using IR spectroscopy, the compatibility between the ingredients was determined. In vivo evaluation of the optimized formulation in comparison to the free TEL was done in hypertension-induced rats, and the systolic blood pressure and all pharmacokinetic parameters were measured. Results: The prepared beads exhibited a high entrapment efficiency percentage, in vitro buoyancy, and prolonged drug release. TEL was compatible with other ingredients, as approved by IR spectroscopy. The prepared TEL beads were spherical, as shown by the SEM. The relative bioavailability of TEL-loaded oil-entrapped beads was 222.52%, which was higher than that of the pure TEL suspension. The prepared TEL beads formulation exhibited a higher antihypertensive effect for a prolonged time compared to pure TEL suspension. Conclusions: It can be concluded that this innovative delivery method of TEL-loaded oil-entrapped beads is a promising tool for enhancing drug solubility and, thus, oral bioavailability and therapeutic efficacy, resulting in enhanced patient compliance. Furthermore, the in vivo study confirmed the formulation’s extended anti-hypertensive activity in animal models.

The coloring behavior of santalin, a natural reddish-brown dye derived from sandalwood, has been investigated in this work for the dyeing of silk fabrics while being heated in MW radiation. Microwave (MW) radiation up to 5 min has been employed to isolate colorant (Santalin) from red sandalwood (Ptrecarpus santalinus) in selected medium, and bio-mordants in competing with salts as chemical-mordants have been included. Statistical analysis was made and dyeing variables were selected for getting dark shades though mordants. MW treatment for 3 min. to both extract and fabric was selected and mild dyeing conditions were optimized statistically to get dark shades. On applying chemical mordants, selected amount of salts of Al+3, Fe+2 and T.A. before and after dyeing, has given good results. Comparatively, selected extracts of plant based sources have shown colorfast shades of high strength. The MW radiation has excellent potential to extract dye form plants using optimum medium through less time and energy, and the application of plant extracts along with sustainable salts have developed colorfast shades.

The environmental transformation and health effects of endocrine disruptors (EDCs) need urgent attention, particularly the formation of transformation products with higher toxicity than parent EDCs. In this paper, an important transformation product dimer (short for ethyl 4-hydroxy-3-(2-((4-hydroxybenzoyl) oxy) ethyl) benzoate) with estrogenic activity was investigated and detected in the photolysis of preservative ethyl-paraben (EPB) dissolved in actual water. The environmental factors, such as the higher initial concentration of EPB, the stronger optical power and the lower pH could stimulate the formation of the dimer. Simultaneously, the interaction of multiple environmental factors was significant, especially the initial concentration and pH using the response surface methodology. Furthermore, the relationship between the environmental factors and the formation of the product dimer was further explained and the empirical model equation was built for predicting the amount of dimer in actual water. Quantum chemical and toxicological calculations showed the estrogenic effect mechanism of the product dimer and it was revealed further that the hydrogen bonds of the dimer and ERα proteins (ARG-394, Glu-353, His-524, GYY-521) were formed, with a lowest binding energy of −8.38 Kcal/mol during molecular docking. In addition, the health effect risk of the product dimer was higher than the parent compound in the blood, cardiovascular system, gastrointestinal system, kidney and liver. In short, the present study was of great significance for the transformation product in pollution control and health effects in the photolysis of EDCs.